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Sunny Shin, Ph.D.
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Professor of Microbiology
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Department: Microbiology
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Graduate Group Affiliations
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- Pharmacology 6b
- Cell and Molecular Biology 5c
- Immunology e
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Contact information
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3610 Hamilton Walk
38 201B Johnson Pavilion
Philadelphia, PA 19104
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38 201B Johnson Pavilion
Philadelphia, PA 19104
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Office: (215) 746-8410
34 Fax: (215) 898-9557
34 Lab: (215) 573-4752
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34 Fax: (215) 898-9557
34 Lab: (215) 573-4752
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Publications
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Education:
21 9 B.S. 2b (Biology, Advisor: Hidde Ploegh) c
3e Massachusetts Institute of Technology, 1998.
21 a Ph.D. 42 (Microbiology and Immunology, Advisor: Yueh-hsiu Chien) c
3f Stanford University School of Medicine, 2004.
21 a Cert. 41 (Unconscious Bias Training: Impact on Decision Making) c
4f University of Pennsylvania Perelman School of Medicine, 2020.
21 a Cert. 35 (Inclusive and Equitable Teaching Seminar) c
55 Center for Teaching and Learning, University of Pennsylvania, 2021.
21 a Cert. 2d (HHMI Gilliam Mentorship Training) c
27 HHMI and CIMER, 2022.
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Permanent link21 9 B.S. 2b (Biology, Advisor: Hidde Ploegh) c
3e Massachusetts Institute of Technology, 1998.
21 a Ph.D. 42 (Microbiology and Immunology, Advisor: Yueh-hsiu Chien) c
3f Stanford University School of Medicine, 2004.
21 a Cert. 41 (Unconscious Bias Training: Impact on Decision Making) c
4f University of Pennsylvania Perelman School of Medicine, 2020.
21 a Cert. 35 (Inclusive and Equitable Teaching Seminar) c
55 Center for Teaching and Learning, University of Pennsylvania, 2021.
21 a Cert. 2d (HHMI Gilliam Mentorship Training) c
27 HHMI and CIMER, 2022.
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1b8 We study innate immunity and host:pathogen interactions using a variety of gram-negative bacteria. We study the intracellular bacterial pathogens Legionella pneumophila, Coxiella burnetii, and Salmonella Typhimurium, and the extracellular pathogen Yersinia pseudotuberculosis using mouse and human model systems with the goal of identifying shared and unique features of innate immunity and bacterial virulence in mice and humans.
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2f6 A major focus of our lab is to understand how the immune system distinguishes between virulent and avirulent bacteria and tailors appropriate antimicrobial responses. One key immune pathway involves the inflammasome, a multi-protein cytosolic complex that activates the host proteases caspase-1, mouse caspase-11, and human caspases-4 and -5 upon cytosolic detection of bacterial products. These caspases mediate the release of IL-1 family cytokines and other inflammatory factors critical for host defense, but overexuberant activation can lead to pathological outcomes such as septic shock. We are currently pursuing how inflammasomes and other cell death pathways are differentially regulated in humans and mice in response to bacterial infection.
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2d6 We are also interested in elucidating how the immune system successfully overcomes the ability of pathogens to suppress critical host functions. We recently found that infected macrophages circumvent Legionella's ability to block host translation by selectively synthesizing and releasing key cytokines. These cytokines then coordinate crosstalk between the alveolar epithelium and bystander immune cells to generate an effective immune response. We also found that dendritic cells undergo cell death in response to Legionella-mediated blockade of host translation. We aim to define additional mechanisms that the immune system uses to detect and overcome pathogen virulence activity to promote antimicrobial defense.
8
136 Insight into these different areas will advance our understanding of bacterial pathogenesis, how the innate immune system distinguishes between virulent and avirulent bacteria and initiates antimicrobial immunity, and will ultimately aid in the design of effective antimicrobial therapies and vaccines.
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6e Prospective students and postdocs are encouraged to contact Dr. Shin to learn more about our research.
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16 Lab personnel:
8
14 Lab manager:
2f Mark Boyer, M.S.- Research Specialist C
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22 Postdoctoral Researchers:
45 Suhas Bobba, Ph.D.- co-mentored with Igor Brodsky; F32 Fellow
2a Mikel Haggadone, Ph.D.- F32 Fellow
4f Matthew Sherman, Ph.D.- co-mentored with Igor Brodsky; Brody fellowship
45 Kimberly Wodzanowki, Ph.D.- Instructor, Department of Biology
58 Ling Wu, M.D., Ph.D.- Pulmonary and Critical Care Instructor, ITMAT KL2 scholar)
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1b Graduate Students:
34 Katie Fox- Master's of Biotechnology Student
4a Alexa Mihaita- CAMB-MVP; co-mentored with Igor Brodsky; NSF Fellow
2c Emily O'Rourke- CAMB-MVP; AHA Fellow
3b Rachel Richards- CAMB-MVP; Penn Presidential Fellow
2c Stephanie Schreiner- IGG; NSF Fellow
5f Jaydeen Sewell, M.S.- CAMB-MVP; IIZD Martin and Pamela Winter Infectious Disease Fellow
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1f Undergraduate Students:
36 Jada Asamoah- Biochemistry Major; FERBS Fellow
3d Salimatou Bah- Health & Societies Major; FERBS Fellow
37 Klarissa Diaz- Neuroscience Major; FERBS Fellow
3a Daniel Getachew- Biophysics Major; Vagelos Scholar
2d Garrett Tishkoff Leach- Biology Major
45 Talia Smith- Biochemistry & Biophysics Major; Vagelos Scholar
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1a Rotation Students:
24 Dylan Luce- CAMB-MVP student
28 Ricardoroman Carale- MSTP student
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Description of Research Expertise
cd My lab is interested in uncovering innate immune mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade host immunity to cause disease.8
1b8 We study innate immunity and host:pathogen interactions using a variety of gram-negative bacteria. We study the intracellular bacterial pathogens Legionella pneumophila, Coxiella burnetii, and Salmonella Typhimurium, and the extracellular pathogen Yersinia pseudotuberculosis using mouse and human model systems with the goal of identifying shared and unique features of innate immunity and bacterial virulence in mice and humans.
8
2f6 A major focus of our lab is to understand how the immune system distinguishes between virulent and avirulent bacteria and tailors appropriate antimicrobial responses. One key immune pathway involves the inflammasome, a multi-protein cytosolic complex that activates the host proteases caspase-1, mouse caspase-11, and human caspases-4 and -5 upon cytosolic detection of bacterial products. These caspases mediate the release of IL-1 family cytokines and other inflammatory factors critical for host defense, but overexuberant activation can lead to pathological outcomes such as septic shock. We are currently pursuing how inflammasomes and other cell death pathways are differentially regulated in humans and mice in response to bacterial infection.
8
2d6 We are also interested in elucidating how the immune system successfully overcomes the ability of pathogens to suppress critical host functions. We recently found that infected macrophages circumvent Legionella's ability to block host translation by selectively synthesizing and releasing key cytokines. These cytokines then coordinate crosstalk between the alveolar epithelium and bystander immune cells to generate an effective immune response. We also found that dendritic cells undergo cell death in response to Legionella-mediated blockade of host translation. We aim to define additional mechanisms that the immune system uses to detect and overcome pathogen virulence activity to promote antimicrobial defense.
8
136 Insight into these different areas will advance our understanding of bacterial pathogenesis, how the innate immune system distinguishes between virulent and avirulent bacteria and initiates antimicrobial immunity, and will ultimately aid in the design of effective antimicrobial therapies and vaccines.
9
6e Prospective students and postdocs are encouraged to contact Dr. Shin to learn more about our research.
8
16 Lab personnel:
8
14 Lab manager:
2f Mark Boyer, M.S.- Research Specialist C
8
22 Postdoctoral Researchers:
45 Suhas Bobba, Ph.D.- co-mentored with Igor Brodsky; F32 Fellow
2a Mikel Haggadone, Ph.D.- F32 Fellow
4f Matthew Sherman, Ph.D.- co-mentored with Igor Brodsky; Brody fellowship
45 Kimberly Wodzanowki, Ph.D.- Instructor, Department of Biology
58 Ling Wu, M.D., Ph.D.- Pulmonary and Critical Care Instructor, ITMAT KL2 scholar)
8
1b Graduate Students:
34 Katie Fox- Master's of Biotechnology Student
4a Alexa Mihaita- CAMB-MVP; co-mentored with Igor Brodsky; NSF Fellow
2c Emily O'Rourke- CAMB-MVP; AHA Fellow
3b Rachel Richards- CAMB-MVP; Penn Presidential Fellow
2c Stephanie Schreiner- IGG; NSF Fellow
5f Jaydeen Sewell, M.S.- CAMB-MVP; IIZD Martin and Pamela Winter Infectious Disease Fellow
8
1f Undergraduate Students:
36 Jada Asamoah- Biochemistry Major; FERBS Fellow
3d Salimatou Bah- Health & Societies Major; FERBS Fellow
37 Klarissa Diaz- Neuroscience Major; FERBS Fellow
3a Daniel Getachew- Biophysics Major; Vagelos Scholar
2d Garrett Tishkoff Leach- Biology Major
45 Talia Smith- Biochemistry & Biophysics Major; Vagelos Scholar
8
1a Rotation Students:
24 Dylan Luce- CAMB-MVP student
28 Ricardoroman Carale- MSTP student
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179 Grayczyk, J.P.^, Liu, L.^, Egan, M.S., Aunins, E., Wynosky-Dolfi, M.A., Canna, S.W., Minn, A.J., Shin, S.*, Brodsky, I.E.*: TLR priming licenses NAIP inflammasome activation by immunoevasive ligands. Proc Natl Acad Sci U S A 121(48): e2412700121, 2024 Notes: ^co-first authors; *co-corresponding authors.
1c0 Akuma, D.C.^, Wodzanowski, K.A.^, Schwartz Wertman, R.^, Exconde, P.M., Vázquez Marrero, V.R., Odunze, C.E., Grubaugh, D., Shin, S.*, Taabazuing, C.*, Brodsky, I.E.*: Catalytic activity and autoprocessing of murine caspase-11 mediate noncanonical inflammasome assembly in response to cytosolic LPS. eLife 13: e83725, 2024 Notes: ^co-first authors; *co-corresponding authors.
1de Matsuda, R.^, Sorobetea, D.^, Zhang, J.^, Peterson, S. T., Grayczyk, J.P., Yost, W., Apenes, N., Kovalik, M.E., Herrmann, B., O’Neill, R.J., Bohrer, A.C., Lanza, M., Assenmacher, C.-A., Mayer-Barber, K.D., Shin, S.*, Brodsky, I.E.*: A TNF-IL-1 circuit controls Yersinia within intestinal pyogranulomas. Journal of Experimental Medicine in press, 2024 Notes: ^co-first authors; *co-corresponding authors.
15a Egan, M.S., O'Rourke, E.A., Kumar Mageswaran, S., Zuo, B., Martynyuk, I., Demissie, T., Hunter, E.N., Bass, A.R., Chang, Y.-W., Brodsky, I.E., and Shin, S.: Inflammasomes primarily restrict cytosolic Salmonella replication within human macrophages. eLife 12(RP90107), 2023.
ed Zhang, J., Brodsky, I.E., and Shin, S.: Yersinia deploys type III-secreted effectors to evade caspase-4 inflammasome activation in human cells. mBio e0131023, 2023.
116 Bass, A.R., Egan, M.S., Alexander-Floyd, J., Lopes Fischer, N., Doerner, J., Shin, S.: Human GBP1 facilitates rupture of the Legionella-containing vacuole and inflammasome activation mBio in press, 2023.
135 Pollock, T.Y., Vazquez Marrero, V.R., Brodsky, I.E., & Shin, S.: TNF licenses macrophages to undergo rapid caspase-1, -11, and -8-mediated cell death that restricts Legionella pneumophila infection. PLOS Pathogens 19(6): e1010767, 2023.
177 Naseer, N.*, Egan, M.*, Reyes Ruiz, V.M.*, Scott, W.P., Hunter, E.N., Demissie, T., Rauch, I., Brodsky, I.E., Shin, S.: Human NAIP/NLRC4 and NLRP3 inflammasomes detect Salmonella type III secretion system activities to restrict intracellular bacterial replication. PLOS Pathogens 18(1): e1009718, 2022.
1b9 Alexander-Floyd, J.^, Bass, A.R.^, Harberts, E.M.^, Grubaugh, D., Buxbaum, J.D., Brodsky, I.E., Ernst, R.K.*, Shin, S.* : Lipid A variants activate human TLR4 and the noncanonical inflammasome differently and require the core oligosaccharide for inflammasome activation. Infection and Immunity 90(8): e0020822, 2022 Notes: ^co-first authors; *co-corresponding authors.
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Selected Publications
134 Nataraj, N.M., Garcia Sillas, R., Herrmann, B.I., Shin, S.*, and Brodsky, I.E.*: Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages. PLOS Pathogens 20(8): e1012469, 2024 Notes: *co-corresponding authors.179 Grayczyk, J.P.^, Liu, L.^, Egan, M.S., Aunins, E., Wynosky-Dolfi, M.A., Canna, S.W., Minn, A.J., Shin, S.*, Brodsky, I.E.*: TLR priming licenses NAIP inflammasome activation by immunoevasive ligands. Proc Natl Acad Sci U S A 121(48): e2412700121, 2024 Notes: ^co-first authors; *co-corresponding authors.
1c0 Akuma, D.C.^, Wodzanowski, K.A.^, Schwartz Wertman, R.^, Exconde, P.M., Vázquez Marrero, V.R., Odunze, C.E., Grubaugh, D., Shin, S.*, Taabazuing, C.*, Brodsky, I.E.*: Catalytic activity and autoprocessing of murine caspase-11 mediate noncanonical inflammasome assembly in response to cytosolic LPS. eLife 13: e83725, 2024 Notes: ^co-first authors; *co-corresponding authors.
1de Matsuda, R.^, Sorobetea, D.^, Zhang, J.^, Peterson, S. T., Grayczyk, J.P., Yost, W., Apenes, N., Kovalik, M.E., Herrmann, B., O’Neill, R.J., Bohrer, A.C., Lanza, M., Assenmacher, C.-A., Mayer-Barber, K.D., Shin, S.*, Brodsky, I.E.*: A TNF-IL-1 circuit controls Yersinia within intestinal pyogranulomas. Journal of Experimental Medicine in press, 2024 Notes: ^co-first authors; *co-corresponding authors.
15a Egan, M.S., O'Rourke, E.A., Kumar Mageswaran, S., Zuo, B., Martynyuk, I., Demissie, T., Hunter, E.N., Bass, A.R., Chang, Y.-W., Brodsky, I.E., and Shin, S.: Inflammasomes primarily restrict cytosolic Salmonella replication within human macrophages. eLife 12(RP90107), 2023.
ed Zhang, J., Brodsky, I.E., and Shin, S.: Yersinia deploys type III-secreted effectors to evade caspase-4 inflammasome activation in human cells. mBio e0131023, 2023.
116 Bass, A.R., Egan, M.S., Alexander-Floyd, J., Lopes Fischer, N., Doerner, J., Shin, S.: Human GBP1 facilitates rupture of the Legionella-containing vacuole and inflammasome activation mBio in press, 2023.
135 Pollock, T.Y., Vazquez Marrero, V.R., Brodsky, I.E., & Shin, S.: TNF licenses macrophages to undergo rapid caspase-1, -11, and -8-mediated cell death that restricts Legionella pneumophila infection. PLOS Pathogens 19(6): e1010767, 2023.
177 Naseer, N.*, Egan, M.*, Reyes Ruiz, V.M.*, Scott, W.P., Hunter, E.N., Demissie, T., Rauch, I., Brodsky, I.E., Shin, S.: Human NAIP/NLRC4 and NLRP3 inflammasomes detect Salmonella type III secretion system activities to restrict intracellular bacterial replication. PLOS Pathogens 18(1): e1009718, 2022.
1b9 Alexander-Floyd, J.^, Bass, A.R.^, Harberts, E.M.^, Grubaugh, D., Buxbaum, J.D., Brodsky, I.E., Ernst, R.K.*, Shin, S.* : Lipid A variants activate human TLR4 and the noncanonical inflammasome differently and require the core oligosaccharide for inflammasome activation. Infection and Immunity 90(8): e0020822, 2022 Notes: ^co-first authors; *co-corresponding authors.
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